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Since the early 1980s the Bahamas has experienced sequential epidemics of freebase/crack cocaine use genital ulcer-inguinal adenopathy disease (GUD) and heterosexual HIV infection. This study aimed to prospectively define the etiology of GUD in patients at the Princess Margaret Hospital during outbreaks of crack cocaine use GUD and HIV infection in the Bahamas. In Nassau 47 consecutive patients with GUD underwent serologic testing for syphilis and for infections with HIV simplex virus type 2 (HSV-2) and Chlamydia trachomatis. Genital ulcer specimens were tested by culture and/or polymerase chain reaction (PCR) assay for Hemophilus ducreyi; by PCR and/or antigen assay for HSV; and by PCR for C trachomatis. Lymph node aspirates were tested by PCR for C trachomatis and H ducreyi. 20 patients (43%) had HIV infection; 8 had lymphogranuloma venereum (LGV) confirmed by PCR detection of C trachomatis sequences consistent with the L2 serovar; and 9 others had possible LGV on the basis of serum microimmunoflourescent C trachomatis antibody titers >or= 256. Inguinal lymphadenopathy or bubo was present in 15 of 17 patients who thus met the laboratory criteria for definite or possible LGV and in 7 of 30 who did not meet such laboratory criteria (P < 0.001). 13 patients had confirmed genital herpes seven had confirmed chancroid and four had probable or possible primary syphilis. The epidemic in the Bahamas of crack use heterosexual HIV infection and GUD apparently included epidemic transmission of LGV. (authors)

Background and Objectives: The development and introduction of nucleic acid amplification (NAA) tests by commercial sources has improved our ability to diagnose chlamydial infections and other sexually transmitted diseases (STDs). A review of approaches to diagnosing STDs can provide a clearer picture of the present needs. Goals: To review the advantage and disadvantages of current and future diagnostic approaches. Study Design: Survey the literature and define current and future needs in developed and developing country settings. Results: The increase in analytical sensitivity afforded by NAA has enabled the use of noninvasive specimens, such as first-void urine (FVU) and self-obtained vaginal swabs, for diagnostic testing and screening asymptomatic low-prevalence populations and hard-to-access populations. This technology allows multiplexing in which targets from multiple agents responsible for a particular syndrome can be amplified and detected. Although NAA tests have been designed to minimize contamination, there is some reluctance to replace less sensitive tests with this new technology. The concerns involve potential false positive and false negative results caused by the presence of inhibitors, even though the rates of false results are low. Other concerns are cost, through-put, hands-on time, and time necessary for results. Conclusions: Nucleic acid amplification tests are a great improvement and additional tests are needed for the diagnosis of STDs at the point of first encounter, with minimal delay between diagnosis and treatment. Affordable tests, which are rapid, sensitive, and specific are needed for use in resource-limited settings where most STDs are seen; this has been a major undertaking for the Sexually Transmitted Diseases Diagnostics Initiative.

While genital ulcers are a risk factor in HIV infection, the association of specific agents of genital ulcer disease (GUD) with HIV infection may vary.To determine the etiology of GUD in HIV-infected and HIV-uninfected men attending sexually transmitted disease (STD) clinics in Durban, Johannesburg, and Cape Town, South Africa, and the association of previous and current sexually transmitted infections with HIV infection in men with ulcerative and nonulcerative STDs.A cross-sectional study of 558 men with genital ulcers and 602 men with urethritis.Patients with GUD were more likely to be infected with HIV than patients with urethritis (39.4% versus 21.4%, Por =0.001). Herpes simplex virus 2 (HSV-2) was the most common agent identified in ulcer specimens (35.9%), and was detected in a significantly higher proportion of ulcer specimens from HIV-infected patients than in specimens from HIV-uninfected patients (47.4% versus 28.2%, Por =0.001). Patients infected with HIV-1 were significantly more likely to have HSV-2 infection, as measured by the presence of the antibody to glycoprotein G-2, than patients not infected with HIV (63.1% versus 38.5%, Por =0.001). Patients infected with HIV-1 were also significantly more likely to have initial HSV-2 infection than HIV-uninfected patients with GUD (50.0% versus 31.6%, P = 0.007). Haemophilus ducreyi was detected in 31.7% of ulcer specimens; prevalence did not vary by HIV-infection status. Treponema pallidum DNA was detected significantly less frequently in ulcer specimens from patients infected with HIV than in specimens from patients not infected with HIV (10.2% versus 26%, Por =0.001); no association was found between HIV-infection status and fluorescent treponemal antibody absorption test seroreactivity, even when men with M-PCR-positive syphilis lesions were excluded from the analyses.The authors found that HSV-2 is a more common etiology of GUD than has been suggested by previous studies conducted in South Africa; serologic evidence of HSV-2 infection and current cases of genital herpes are strongly associated with HIV infection among men who present to STD clinics with GUD or urethritis.

Background and objectives Epidemiologic studies on syphilis have been hampered by the fact that strains of Treponema pallidum subspecies pallidum (T. pallidum), the causative agent of this disease, cannot be differentiated by either protein-based or deoxyribonucleic acid-based methods. Syphilis is endemic in many developing countries and is common in some industrialized nations. In addition, the disease has been shown to increase the risk of infection with the human immunodeficiency virus. Goal To develop a molecular subtyping method for T. pallidum. Study design Two genes exhibiting intrastrain variability were identified as potential targets for strain differentiation: the acidic repeat protein (arp) gene, which contains a variable number of 60 base pair repeats, and a member of the treponema pallidum repeat (tpr) gene family. Polymerase chain reaction amplification and restriction endonuclease digestion of polymerase chain reaction products from laboratory strains and clinical specimens were used to develop a molecular subtyping scheme for T. pallidum. Results Determining the number of repeats in the arp gene by polymerase chain reaction resulted in 12 different subtypes among the 63 isolates that were studied. Among those, most (54.2%) had arp genes with 14 repeats. The other 11 subtypes had arp genes with 7 to 21 repeats, each accounting for 2% to 14% of the isolates. Polymerase chain reaction amplification of a member of the tpr gene family from a subset of 46 isolates followed by digestion of the polymerase chain reaction product with MseI resulted in seven restriction fragment length polymorphism patterns designated a to g. Strains with 14 repeats could be grouped into five restriction fragment length polymorphism subtypes. By combining the two systems we observed 16 subtypes among 46 isolates examined. This typing system is stable, reproducible, and easy to perform. In addition, the use of the ABI Genetic Analyzer for the determination of fragment size and banding patterns makes the results unbiased. Conclusion This is the first molecular subtyping system that distinguishes among clinical isolates of T. pallidum.

Background and objectives The diagnosis of many sexually transmitted diseases (STD) requires laboratory testing. The authors assessed the effects of the introduction of new tests and regulations on STD testing. Study design A questionnaire survey was mailed to a random sample of facilities listed in the STD Referral Database inquiring about tests offered, changes in testing, and reasons for changes. Results Responses from 405 facilities were analyzed. Most responding facilities collected specimens for nontreponemal tests for syphilis (352 of 405 [86.9%]). Since each facility's information was last updated, the number reporting testing for Chlamydia trachomatis rose from 160 of 405 (39.5%) to 288 of 405 (71.1%), but testing for gonorrhea and chancroid decreased (365 of 405 [90.1%] to 328 of 405 [81%], and 182 of 405 [44.9%] to 32 of 405 [7.9%], respectively). Of 364 responses to a question on changes in tests performed in the last 2 years, 249 (68.4%) reported no change, 81 (22.3%) reported an increase, and 37 (10.2%) reported a decrease. The most frequently added tests were nonculture tests for C. trachomatis (34 of 81 [42%]) and the most frequent reason for adding tests was targeted funding (25 of 81 [30.9%]). The most frequently discontinued tests were cultures and gram stains for gonorrhea (15 of 37 [40.5%]) and other in-house tests (9 of 37 [24.3%]). Most facilities that discontinued testing cited the Clinical Laboratory Improvement Act as the reason (34 of 37 [91.9%]; 95% confidence interval = 78.1%, 98.3%). Conclusions The number of facilities testing for C. trachomatis has increased with funding and with the availability of nonculture tests, but the number of those testing for chancroid and gonorrhea has decreased. Implementation of the Clinical Laboratory Improvement Act may be associated with a decrease in the number of facilities performing tests for STD.

We characterized 475 non-beta-lactamase-producing gonococcal isolates from five U.S. cities by auxotype, serovar, and plasmid content to determine the frequency of isolates with the 24.5-Mdal gonococcal conjugative plasmid. A total of 150 (32%) of all isolates possessed the 24.5-Mdal plasmid; these isolates represented between 10% and 53% of isolates from each city. Isolates possessing the 24.5-Mdal plasmid belonged to 45 (56%) of 81 auxotype/serovar (A/S) classes, or between 24% and 70% of the A/S classes isolated in each city. Overall, a higher proportion of strains isolated in the southern cities possessed the 24.5-Mdal plasmid than did those from northeastern or northwestern cities. These strains appear to have spread independently of the spread of beta-lactamase-producing Neisseria gonorrhoeae strains. The prevalence of N. gonorrhoeae strains with the 24.5-Mdal conjugative plasmid has increased substantially and may have important implications for the epidemiology of gonorrhea caused by beta-lactamase-producing strains.

In recent years the emergence and spread of antibiotic resistance in Neisseria gonorrhoeae has increased markedly. Chromosomal resistance to penicillin and tetracycline is due to the effects of one or more mutations and is generally low-level. However, the effects of these mutations are additive. Thus, the level of resistance in strains with several mutations is often high enough to yield significant rates of treatment failure. Resistance to aminoglycosides (e.g., streptomycin and kanamycin) and spectinomycin, an aminocyclitol antibiotic is not due to the inactivation of the antibiotic but to an alteration in the sensitivity of the 30S ribosomal subunit to the drug. At least five beta-lactamase plasmids of N. gonorrhoeae have been described. Some of these plasmids can be mobilized by the 24.5-MDa gonococcal conjugative plasmid and transferred to other gonococcal strains. Gonococci have recently acquired high-level resistance to tetracycline due to the streptococcal tetM determinant. This determinant is located on a 25.2-MDa plasmid that possesses a considerable degree of homology with the 24.5-MDa conjugative plasmid. The 25.2-MDa plasmid has retained the ability to transfer beta-lactamase plasmids as well as to mobilize and transfer itself to suitable recipient strains.

First-catch urine specimens were obtained before clinical examination from 101 sexually active men who attended a sexually transmitted diseases clinic with a complaint of urethral discharge. Urethral swab specimens were used for preparation of smears and were then cultured on Martin-Lewis medium. Enzyme immunoassay (EIA) tests were performed on (1) uncentrifuged urine, (2) urine sediment, and (3) urine sediment diluted 1:6 with detergent buffer. Urethral cultures from 65 (64%) of the 101 men were positive for N. gonorrhoeae. EIA performed on urine sediment diluted 1:6 yielded the highest sensitivity: 98.5% (64/65). Sensitivity of EIA for uncentrifuged urine was only 66% (43/65). Specificity of all samples tested exceeded 97.2%. Overall agreement between results of EIA on diluted urine sediment and culture was 98% (99/101). Discordant culture and EIA results were unrelated to urine volume, time since prior urination, quantity of gonococcal growth on Martin-Lewis medium, duration of urine storage (less than 72 hours) before testing, or immunotype. EIA tests using urine sediment are highly sensitive and specific, and they offer an alternative means of diagnosing gonorrhea in men who refuse urethral manipulation. They also provide a means of screening men at high risk for gonorrhea who have submitted a urine specimen for other reasons.